This Program Project will examine the structure and function of proteins found in the alphavirus and flavivirus genera. These viruses constitute important human pathogens and include members such as dengue and West Nile as well as potential bioterrorist weapons like Venezuelan equine encephalitis and tick-borne encephalitis virus. The experiments that are proposed require significant shared resources to accomplish the objectives that are listed in the Introduction to this proposal. The Purdue Structural Biology Group has established these shared resources over many years. The funds requested for these facilities are required for their usage and maintenance on projects directly related to the Program Project. These facilities include X-ray, EM, cell and virus culture, computing, and administrative components. To take advantage of emerging technologies that directly impact these structure-function studies, we also seek funds to establish and maintain a new facility that will enable the Principal Investigators to carry out high-throughput approaches to cloning, protein expression, crystallization, and mutagenesis. The functions of each of these facilities are detailed in this Core Proposal. The facilities described in this Core are absolutely essential for the success of the individual R01 research proposals.